Previous studies by several investigators have demonstrated in hypertensive subjects a humoral agent which increases vascular reactivity to vasoconstrictors (vascular sensitizing factor, VSF). It has been suggested that the VSF observed in hypertensive subjects might be the putative natriuretic hormone (NH). Accordingly, we propose to determine whether extracts of plasma which have been shown to contain NH can also be shown to contain a VSF. Plasma obtained from volume expanded and hydropenic dogs is processed for extraction of NH by our previously described methods. Final extraction is by high performance liquid chromatography (HPLC). The effect of HPLC fractions on vascular sensitivity to vasoconstrictors will be tested on two preparations: the cremaster muscle and the isolated hind limb. In the former, changes in arteriolar diameter in response to vasoconstrictors are observed directly. In the latter, sensitivity of the microcirculation to vasoconstrictors is determined indirectly by changes in flow in a constant pressure preparation or changes in pressure in a constant flow preparation. The possible role of this factor in hypertension will be explored. Rats will be made hypertensive by administration of deoxycorticosterone (DOC) and saline. Once hypertension is established, blood will be collected and assayed for VSF activity and NH activity. The demonstration that plasma extracts of volume expanded dogs increases sensitivity of the microcirculation to vasoconstrictors would strongly suggest that NH is a vascular sensitizing factor, which could play a role in salt induced hypertension.